W26052102 Imbokodo & Mosaico updates, plans for correlates and sieve analyses.

Summary

The script discusses an extensive public-private partnership working on a global prophylactic HIV vaccine. The goal is to develop a vaccine effective against diverse HIV strains, using mosaic antigen designs. Two ongoing efficacy studies, Imbokoto and Mosaico, are evaluating the vaccine in different populations and transmission modes. The studies involve immunogenicity evaluations, sieve analysis, and immune bridging to support a broad evidence package. The aim is to identify immune markers associated with vaccine efficacy and understand how and where the vaccine could be used globally.

Takeaways

• 🌐 The program aims to develop a global prophylactic vaccine for HIV, targeting diverse strains worldwide, not just strain or plate-specific vaccines.
• 🔬 Mosaic antigen designs by Betty Gorber are central to the vaccine development, using a heterologous regimen for delivery.
• 📚 Two ongoing efficacy studies, Imbokoto and Mosaico, are complementary and focus on different HIV clades and transmission modes.
• 📊 Imbokoto is conducted in Southern Africa with a focus on clade C viruses, while Mosaico evaluates in the Americas and Europe, focusing on clade B.
• 👥 The studies involve different demographics: Imbokoto targets young women (18-35), whereas Mosaico includes MSM and transgender individuals (18-60).
• 💉 The vaccine regimen involves multiple vaccinations with different components to enhance immune responses against various HIV strains.
• 🧬 Sieve analysis is being conducted to understand the vaccine's effect on viral gene sequences and to identify mechanisms of an imperfect vaccine regimen.
• 🔄 Immunobridging studies are necessary to connect the efficacy of the vaccine regimens across different studies and populations.
• 📈 A pilot immunogenicity study is underway in the Imbokoto study to characterize vaccine responses in the study population and identify potential predictors of immune responses.
• 🧬 Future immune and correlates analyses in the Mosaico study will build upon the findings and learnings from the Imbokoto study.
• 🌟 The ultimate goal is to identify strong immunologic markers associated with vaccine efficacy, which could help define the use of such vaccines globally.

Q & A

What is the primary goal of the HIV vaccine program mentioned in the transcript?

The primary goal of the program is to develop a global prophylactic vaccine that is not strain or plate-specific but is relevant for the globally diverse strains of HIV, based on mosaic antigen designs.

Who developed the mosaic antigen designs used in the vaccine?

Betty Gorber developed the mosaic antigen designs used in the vaccine.

What is the significance of a heterologous vaccine regimen in the context of this program?

A heterologous vaccine regimen is used to deliver the mosaic antigens and for Gag, Pol, and Env, which are coated by Ad26, as well as soluble trimeric gp-140, to enhance the vaccine's efficacy.

What are the two ongoing efficacy studies mentioned in the transcript?

The two ongoing efficacy studies are the Imbokoto study, which uses the vaccine HBTN705, and the Mosaico study, which uses the vaccine HBTN706.

In which regions are the Imbokoto and Mosaico studies taking place?

The Imbokoto study is taking place in five countries in Southern Africa, while the Mosaico study is conducted throughout the Americas and Europe.

What is the predominant virus clade circulating in the Impacto study?

Clade C is the predominant virus circulating in the Impacto study.

What are the differences in the study designs between Imbokoto and Mosaico?

Both studies have a similar design with a one-to-one randomization and participants receiving two vaccinations. The difference is that in Mosaico, the third and fourth vaccinations also include the mosaic gp-140 component to expand immune responses.

What is the purpose of the immunobridging studies mentioned in the transcript?

The immunobridging studies aim to support a broad evidence package for the use of the vaccines by bridging between different vaccine regimens, populations, and plates to show the vaccine's efficacy across various conditions.

What are the objectives of the pilot immunogenicity study currently taking place in the Imbokoto study?

The pilot immunogenicity study aims to characterize the immunogenicity of the vaccine regimen in the study population, understand the temporal relationships between immune responses, and develop predictors of immune responses to inform future analyses.

What is the sieve analysis, and how does it contribute to the vaccine program?

The sieve analysis involves sequencing all viral genes encoded in the vaccine to characterize differences between virus sequences in the study arms. It helps elucidate the mechanisms of an imperfect vaccine regimen and guides future iterations and hypotheses for immune correlance analyses.

How do the results from the Imbokoto study plan to inform the Mosaico study?

The results from the Imbokoto study will allow for the definition and testing of specific correlates hypotheses in the Mosaico study, helping to identify immune markers associated with risk of infection and defining the use of the vaccine.

What is the hypothesis regarding the extrapolation of vaccine efficacy to other HIV clades?

The hypothesis is that if efficacy can be demonstrated and similar levels of immune responses are seen across clades, then the vaccine could also prevent infection by other diverse strains of HIV, which needs to be supported by strong immunologic markers associated with vaccine efficacy.

Outlines

00:00

🌐 Global HIV Vaccine Development

The script discusses the development of a global prophylactic HIV vaccine, emphasizing a public-private partnership effort spanning 12 years. The goal is to create a vaccine effective against diverse HIV strains worldwide, not just specific ones. The vaccine strategy involves mosaic antigen designs by Betty Gorber and a heterologous regimen with different components like Ad26 and soluble trimeric gp-140. The script also outlines two ongoing efficacy studies, Imbakoro and Mosaico, which aim to cover a wide range of HIV clades and transmission modes. The studies are designed to evaluate the vaccine's efficacy in different populations and regions, with a focus on intravaginal and interrectal transmission. The summary also mentions the importance of immunobridging studies to support a broad evidence package for vaccine use.

05:02

🧬 Immunogenicity Evaluations and Correlates of Protection

This paragraph delves into the ongoing pilot study within the Imbokoto trial, focusing on characterizing the immunogenicity of the vaccine regimen in the study population. The aim is to understand the temporal relationship between immune responses and factors influencing them at baseline and post-vaccination. The study seeks to develop predictors of immune responses and select unique markers for case-control endpoints in correlates of protection analysis. It also includes a detailed look at various types of immune responses, such as binding antibodies, IgG3, IgA, phagocytosis, cytotoxicity, and T-cell functionality. Additionally, the script describes the sieve analysis to characterize viral gene differences between study arms and the mechanisms of an imperfect vaccine regimen. The paragraph concludes with plans for immune and correlates analyses in the Mosaico study, building on lessons from previous studies like RP144, 505 studies, and NHP challenge studies.

10:03

🤝 Acknowledging Partners in HIV Vaccine Research

The final paragraph is a brief acknowledgment of the various partners involved in the HIV vaccine research program. It expresses gratitude to longstanding partners, the development team at Johnson & Johnson, clinical teams, leadership, and the sites and teams from both the Imbokoto and Mosaico studies. The speaker thanks the audience for their attention, highlighting the collaborative nature of the research efforts.

Keywords

💡HIV Vaccine

An HIV vaccine is a prophylactic that aims to prevent infection by the human immunodeficiency virus (HIV). In the video's context, the goal is to develop a global prophylactic vaccine that is effective against the diverse strains of HIV worldwide. The script mentions a mosaic antigen design strategy to achieve this, indicating the vaccine's broad applicability.

💡Mosaic Antigen

Mosaic antigens are a type of vaccine component that combines elements from various strains of a virus to create a broad immune response. The script refers to mosaic antigen designs developed by Betty Korber, which are intended to provide coverage against a wide range of HIV strains, not just a single or a few specific strains.

💡Heterologous Vaccine Regimen

A heterologous vaccine regimen involves the use of different types of vaccines or different forms of the same vaccine in a sequence to enhance the immune response. The script describes the use of this approach with mosaic antigens and other components like Ad26 and soluble trimeric gp-140 to improve vaccine efficacy.

💡Clades

In the context of the video, clades refer to the genetic groupings of HIV strains. The script mentions concerns about clade diversity, indicating the importance of a vaccine that is effective against multiple strains of HIV, which are categorized into different clades based on their genetic similarities.

💡Modes of Transmission

Modes of transmission refer to the various ways in which a disease can spread from one individual to another. The script discusses the importance of a vaccine being effective against multiple modes of HIV transmission, such as intravaginal and interrectal transmission, to provide comprehensive protection.

💡Efficacy Studies

Efficacy studies are clinical trials designed to evaluate how well a vaccine works in preventing a disease. The script mentions two ongoing efficacy studies, Imbokoto and Mosaico, which are testing the vaccine's effectiveness in different populations and settings.

💡Immunogenicity

Immunogenicity refers to the ability of a vaccine to provoke an immune response. The script discusses pilot studies aimed at characterizing the immunogenicity of the vaccine regimen in the study population, which is crucial for understanding how the vaccine may protect against HIV.

💡Correlates of Protection

Correlates of protection are immune responses or markers that are associated with a vaccine's ability to prevent disease. The script describes an effort to identify these correlates for the HIV vaccine, which would help in understanding what immune responses are necessary for protection.

💡Vector Immunity

Vector immunity refers to the immune response generated against the delivery vehicle used in a vaccine, such as the adenovirus vector in the case of Ad26. The script mentions evaluating pre-existing vector immunity, which could impact the vaccine's effectiveness.

💡Sieve Analysis

Sieve analysis involves examining viral sequences to identify specific mutations or patterns that may be associated with vaccine-induced immunity. The script discusses conducting a sieve analysis for infections that occur during the study to understand the vaccine's impact on viral evolution.

💡Extrapolation

Extrapolation in the context of the video refers to the process of extending the findings from one group or clade to other groups or clades. The script talks about the possibility of extrapolating vaccine efficacy from the clades tested in the trials to other HIV clades, which would imply broader vaccine applicability.

Highlights

The program aims to develop a global prophylactic vaccine for HIV, not strain or plate-specific, but relevant for diverse strains worldwide.

The vaccine is based on mosaic antigen designs by Betty Korber, delivered through a heterologous regimen.

The vaccine development involves a public-private partnership effort spanning over 12 years.

Two ongoing efficacy studies, Imbokoto and Mosaico, are evaluating the vaccine in different regions and populations.

Imbokoto focuses on HIV clade C in southern Africa, while Mosaico evaluates clade B in the Americas and Europe.

Different modes of transmission are considered in the studies: intravaginal for Imbokoto and interrectal for Mosaico.

The study design includes a 1:1 randomization with participants receiving multiple vaccinations and follow-ups.

Mosaico includes the mosaic gp-140 component to expand immune responses against diverse clades.

Immunobridging studies are conducted to show the vaccine's efficacy across different regimens and populations.

A pilot study in the Imbokoto trial is characterizing the immunogenicity of the vaccine regimen in the study population.

Temporal relationships between immune responses and factors influencing them are being analyzed.

Development of predictors of immune responses, such as neutralizing antibodies, age, or body mass index, is underway.

The pilot study aims to identify unique markers for inclusion in the first tier of case control endpoints.

Sieve analysis is initiated to characterize differences between viral sequences in the study arms.

Learnings from previous clinical studies, such as RP144 and NHP challenge studies, guide the current approach.

The goal is to identify immune markers associated with risk of infection to define the vaccine's utility.

If efficacy is demonstrated, the hypothesis is to extrapolate protection to other HIV clades and transmission modes.

Strong immunologic markers are needed to support the extrapolation of vaccine efficacy to diverse HIV strains.

Transcripts

[Music]

hpx2008 and hp 10705

we also have uh other names in bokodo

um hbtn706 also mosaico

that's sometimes easier for people to

worry about and we'll

uh show you the current i um thinking on

our plans for correlates and civ

analyses in this program

so all of this work is a part of a very

uh extensive public private

partnership effort with with many people

who've been involved in this program

um over its uh last 12 years

and our goal is is not to work on a

strain specific or plate-specific

vaccine but a global prophylactic

vaccine that'll

be relevant for the globally diverse

strains of hiv

and that's based on mosaic antigen

designs developed by betty gorber

and those are delivered through the use

of a heterologous vaccine regimen

with the mosaic antigens and for gag

paul and on been coated by add26

as well as soluble trimeric gp-140

envelope peruvians

so in consideration of evaluating

efficacy we're obviously worried about

clade diversity

but also making sure that vaccines are

relevant against multiple modes of

transmission

and also valuable in the

context where prep is widely used

um so currently for this program there's

two complementary efficacy studies

ongoing

um seven of hbtn705 is in vocoder

706 is mosaico um imbakoro's in

five countries in southern africa

whereas mosaic goes

throughout the americas and europe uh

clade c is the predominant uh viruses

circulating

in the impacto study whereas in mosaic b

will evaluate heterosexual young women

um

age 18 to 35 well compared to

msm and transgender individuals 18 up to

60 years old

and the modes of transmission between

these two are also different it'll be

primarily intravaginal transmission

uh versus interrectal transmission so

combined between these two studies

though

there is a good coverage

for both the uh major clades that are

circulating globally

as well as the major uh populations

and uh routes of transmission that need

to be addressed

uh mosaico this is a quick overview of

the study design

it's a one-to-one randomization

participants get two vaccinations

either with the um tetravalent

at 26 mosaic followed by two more

vaccinations in one

six and 12 with the add 26 mosaics

combined

and clad cgp140 they're followed up to

month 24

and then in a stage 2 analysis until

month 36.

mosaico has very much the same design um

the only difference is that in the third

and fourth vaccinations

uh there's also the inclusion of the

mosaic gp-140 component

this was shown to expand the clade b

and non-clade c immune responses

without while not interfering with the

clad c responses so we think this will

be a better

um antigen combination for a for a

globally useful vaccine

so there's also different types of um

immunobridging so these two studies will

evaluate if the vaccines are efficacious

in specific populations

um but in order to support a broad

evidence package for the use of these

vaccines

uh we need to conduct studies that will

bridge between these two regiments

to show that what happens with the

regiment in mosaico

is also relevant for the regiment used

in the

invocative study we need to bridge

between populations to show that

uh protection that would be relevant uh

occur in

young women in southern africa is also

relevant for young women in other parts

of the world

also to bridge between plates to show

that if we can protect

uh with these regimens from uh clay b

and mosaico

that other msm and transgender

individual populations could also be

protected

in other parts of the world we're not

going to be able to bridge formally

between modes of transmission

but given that the the modes of

transmission that are being studied are

those that are

uh generally the higher risk of

infection for exposure we think that it

would

be reasonable to to argue that

meeting a high bar for transmission risk

would also protect against other

other modes of transmission

so in currently in terms of what's going

on in the invocoto study immunogenicity

valuations there's a pilot

study to characterize the um well

there's four

four objectives of it um this is

occurring right now

while the um while the follow-up stage

of the

[Music]

study is still ongoing we're going to

characterize the immunogenicity back

of the vaccine regimen in the study

population

so we've compared the we've

characterized the immunogenicity of this

vaccine regimen in general

but we need to understand how it

actually behaves

in this population uh we want to

understand the

the temporal relationships between the

immune responses

um factors that could influence immune

responses at baseline

then post third post fourth vaccination

and then one year after the vaccination

to see how

those responses relate to one another

that'll be informative for any

um time-dependent correlates of

protection analyses that could be

conducted later on

we also need to develop best possible

predictors of immune responses

such as you might consider at 26

neutralizing antibody as a

as an example of a potential baseline

predictor or

age or body mass index or things like

this

and also based on these pilot study

results we'll be able to down select the

unique markers

that'll be included in the in the first

tier of

case control endpoints for the

correlates of protection analysis

so these are the currently planned um

pilot immunogenicity evaluations

looking at binding antibodies to the

vaccine-matched envelopes

bama and the uh bama antigens against uh

sets of uh clad c envelopes um looking

at igg3

iga and igg responses phagocytosis

responses

um cytotoxicity responses um in the

infected cell assays

uh the cd4 and cd8 functionality

as well as t-cell breath evaluations by

elie spot

and um ellie spot will also look at

the responses to the pte peptides that

were used um to help design the the

mosaic antigens

and we'll also evaluate the pre-existing

vector immunity

um in parallel we're also initiating the

sieve analysis

for infections that occur throughout the

first stage of the study

so we'll sequence all the viral genes

that are encoded in the vaccine so gag

paul and on

this will help characterize differences

between the

virus sequences that occur in the two

study arms so we can see if there's

differences in the number of

founding viruses distance to the

vaccines

if there's specific sieve effects on

that are

elicited by the vaccine and this will

help elucidate

the mechanisms of an imperfect vaccine

regimen and

that will also then uh guide future

iterations

and more specific hypotheses that can be

tested in immune correlance analyses

so and then thinking uh further along

the mosaic

study is still enrolling but eventually

that

study will need to uh also conduct

immune and correlates analyses and we

want to do that

having learned as much as we can from in

bukota at the time

so everything that we've learned from

invocodo or that we're planning on for

invocoto is based on what we've learned

through the previous clinical studies

uh most through rp144 the

um 505 studies the step studies

um as well as the nhp challenge studies

so all of the learnings that we've

uh taken from these will hopefully

give us the best possible chance to

identify the immune markers that can be

associated with risk as an infection

and help define exactly when

and where and how a vaccine like this

could be used

so also when we do have uh results from

invocoto

this will then allow a specific set of

correlates hypotheses to be defined and

tested in mosaica

um so beyond the two efficacy studies

who will also want to explore if it's

possible to extrapolate

from the clades against hiv is evaluated

to other clades of hiv

where our hypothesis is if efficacy is

can be demonstrated and we see similar

levels of immune responses across glades

then we'd like to infer that vaccine

could also prevent infection

of those diverse trades in hiv and that

needs to be supported by

the identification of strong immunologic

markers that are associated with

uh vaccine efficacy so um

if imbakoto would demonstrate efficacy

in young women

then we'd have to be able to establish

hopefully

that other clades could also be

protected

from vatican transmission and

correspondingly mosaico

would also establish that efficacy for

clay b

and other clade protection could also be

inferred for intrarective transmission

so i just stopped by thanking all our

partners

many of our long-standing partners our

johnson ganton development team

uh clinical team and our leadership

the imbokoto uh all of the invocodo

sites

mosaico teams and

thank you for for your attention